Grüsser SM, Wrase J, Klein S, Hermann D, Smolka MN, Ruf M et al. Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics. Psychopharmacology (Berl) 175: 296-302

Department of Medical Psychology, Campus Charité Mitte, Charité--University Medicine Berlin, Berlin, Germany.
Psychopharmacology (Impact Factor: 3.88). 10/2004; 175(3):296-302. DOI: 10.1007/s00213-004-1828-4
Source: PubMed


Animal experiments have provided evidence that the striatum and medial prefrontal cortex play a predominant role in the acquisition and maintenance of drug-seeking behavior.
Alcohol-associated stimuli that were regularly paired with alcohol intake may become conditioned cues and elicit a motivational response that triggers relapse in alcohol-dependent patients.
We used functional magnetic resonance imaging and visual alcohol-associated and control cues to assess brain activation in ten abstinent alcoholics and control subjects. Patients were followed for 3 months, and alcohol intake was recorded.
Alcohol-related versus neutral visual stimuli activated the putamen, anterior cingulate and adjacent medial prefrontal cortex in alcoholics compared with healthy controls. Cue-induced activation of these brain areas was pronounced in the five alcoholics who subsequently relapsed during the observation period. A multiple regression analysis showed that, in alcoholics, the amount of subsequent alcohol intake was associated with the intensity of cue-induced brain activation but not the severity of alcohol craving, amount of previous alcohol intake or duration of abstinence before scanning.
This pilot study showed that cue-induced activation of the anterior cingulate, medial prefrontal cortex and striatum may play a role in the attribution of incentive salience to alcohol-associated stimuli, thus increasing the motivational value and attentional processing of alcohol cues. Functional brain imaging may help to identify a group of alcoholics with an otherwise undetected high risk of relapse.

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    • "The sample we analyzed in order to address our main research question consisted of 16 patients in the DCS group and 16 control patients. In previous fMRI studies on cue reactivity, similar sample sizes had sufficient power to obtain group activations as well as group differences (Grüsser et al. 2004; Hermann et al. 2006). The groups did not differ at baseline in terms of any of the variables reported in Table 1. "
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    ABSTRACT: Mesocorticolimbic reactivity to alcohol-associated cues has been shown to be associated with relapse to renewed drinking and to be decreased by cue-exposure-based extinction training (CET). Evidence from preclinical studies suggests that the extinction of conditioned alcohol-seeking behavior might be facilitated by drugs increasing N-methyl-D-aspartate (NMDA) receptor-associated memory consolidation. In this study, we assessed the efficacy of CET treatment supplemented with the partial NMDA-receptor agonist D-cycloserine (DCS) at reducing mesolimbic cue reactivity (CR), craving, and relapse risk in alcoholism. In a randomized, placebo-controlled, double-blind study, we recruited 76 recently detoxified abstinent alcohol-dependent patients. Thirty-two (16 DCS, 16 placebo) patients showed cue-induced ventral-striatal activation measured with functional magnetic resonance imaging (fMRI) prior to treatment and were thus included in the efficacy analyses. After inpatient detoxification, patients underwent nine sessions of CET spaced over 3 weeks, receiving either 50 mg DCS or placebo 1 h prior to each CET session. FMRI was conducted before treatment and 3 weeks after treatment onset. Following treatment with CET plus DCS, cue-induced brain activation in the ventral and dorsal striatum was decreased compared to treatment with CET plus placebo. Elevated posttreatment ventral striatal CR and increased craving (assessed using the Obsessive Compulsive Drinking Scale) were associated with increased relapse risk. DCS was shown to augment the effect of CET for alcohol-dependent subjects. The interaction between craving and ventral-striatal CR on treatment outcome suggests that CET might be especially effective in patients exhibiting both high craving and elevated CR.
    Psychopharmacology 07/2015; 232(13):2353-2362. DOI:10.1007/s00213-015-3882-5 · 3.88 Impact Factor
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    • "Alcohol-related stimuli can then act as predictors of reward and as incentive stimuli motivating and controlling behavior (Flagel et al. 2011). Indeed, even in the absence of a significant pharmacological effect, conditioned cues can elicit striatal dopamine release in humans (beer flavor cues: Oberlin et al. 2013) and dopaminergic striatal activity (alcohol picture cue: Grüsser et al. 2004; Heinz et al. 2004; Vollstädt-Klein et al. 2010). In heavy drinkers, enhanced attentional biases toward conditioned alcohol cues have been linked to alcohol craving and alcohol seeking behavior (Dickter et al. 2013). "
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    ABSTRACT: Abstract Heightened neural responsiveness of alcoholics to alcohol cues and social emotion may impede sobriety. To test mesocorticolimbic network responsivity, 10 (8 men) alcohol use disorder (AUD) patients sober for 3 weeks to 10 months and 11 (8 men) controls underwent fMRI whilst viewing pictures of alcohol and non-alcohol beverages and of emotional faces (happy, sad, angry). AUD and controls showed similarities in mesocorticolimbic activity: both groups activated fusiform for emotional faces and hippocampal and pallidum regions during alcohol picture processing. In AUD, less fusiform activity to emotional faces and more pallidum activity to alcohol pictures were associated with longer sobriety. Using graph theory-based network efficiency measures to specify the role of the mesocorticolimbic network nodes for emotion and reward in sober AUD revealed that the left hippocampus was less efficiently connected with the other task-activated network regions in AUD than controls when viewing emotional faces, while the pallidum was more efficiently connected when viewing alcohol beverages. Together our findings identified lower occipito-temporal sensitivity to emotional faces and enhanced striatal sensitivity to alcohol stimuli in AUD than controls. Considering the role of the striatum in encoding reward, its activation enhancement with longer sobriety may reflect adaptive neural changes in the first year of drinking cessation and mesocorticolimbic system vulnerability for encoding emotional salience and reward potentially affecting executive
    Brain Imaging and Behavior 04/2015; DOI:10.1007/s11682-015-9374-8 · 4.60 Impact Factor
    • "Here, we therefore examined the relationship between the NAcc activation, PIT, relapse and drinking behavior in alcohol-dependent patients after detoxification. We focused our imaging analysis on the NAcc as a predefined anatomical region of interest (ROI) because it has been associated with the reinforcement learning system (Flagel et al. 2011; Lesaint et al. 2014), human PIT (Talmi et al. 2008; Geurts et al. 2013), dopamine and alcohol dependence (Heinz et al. 2004, 2005), and has been reported to covary with relapse risk in alcohol dependence (Grüsser et al. 2004). Other known risk factors for relapse include craving (Bottlender & Soyka 2004; Adamson, Sellman & Frampton 2009), severity of alcohol dependence (McLellan et al. 1994; Langenbucher et al. 1996; Staines et al. 2003; Adamson et al. 2009) and smoking (Gulliver et al. 1995). "
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    ABSTRACT: In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. © 2015 Society for the Study of Addiction.
    Addiction Biology 04/2015; DOI:10.1111/adb.12243 · 5.36 Impact Factor
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